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Overexpression of the MYC oncogene is a molecular hallmark of both cancer initiation and progression. Targeting MYC is a logical and effective cancer therapeutic strategy. A special DNA secondary structure, the G-quadruplex (G4), is formed within the nuclease hypersensitivity element III 1 (NHE III 1 ) region, located upstream of the MYC gene's P1 promoter that drives the majority of its transcription. Targeting such G4 structures has been a focus of anticancer therapies in recent decades. Thus, a comprehensive review of the MYC G4 structure and its role as a potential therapeutic target is timely. In this review, we first outline the discovery of the MYC G4 structure and evidence of its formation in vitro and in cells. Then, we describe the functional role of G4 in regulating MYC gene expression. We also summarize three types of MYC G4-interacting proteins that can promote, stabilize and unwind G4 structures. Finally, we discuss G4-binding molecules and the anticancer activities of G4-stabilizing ligands, including small molecular compounds and peptides, and assess their potential as novel anticancer therapeutics., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study is aimed to investigate whether Mabuterol (Mab) inhibits proliferation of airway smooth muscle cells (ASMCs) induced by platelet-derived growth factor BB (PDGF-BB) and how far it is related to mitochondrial fission/fusion and intracellular calcium if it comes into play. To explore the mechanism of Mab's antagonizing the proliferation, Mdivi-1, DRP1 inhibitor, which has an inhibitory effect on mitochondrial fission, is used to compare with Mab. Cell viability was measured by either MTT or CCK-8. The inhibitory effect of Mab on S phase of ASM cell cycle induced by PDGF-BB was analyzed by flow cytometry (FCM). Fluo-3/AM, Ca 2+ fluorescent probe, was used to detect Ca 2+ fluorescence intensity by inverted microscope and flow cytometry. The gene expression of Drp-1 and Mfn-2 was observed with Real time PCR and the proteins of Drp-1, Mfn-2, PCNA and cyclin D1 were assessed by Western Blot. Mab and Mdivi-1 both suppressed the proliferation induced by PDGF-BB. The results from inverted microscope and flow cytometry showed that Mab inhibited [Ca 2+ ]i in rat ASMCs induced by PDGF-BB. Cell cycle concept map illustrated that Mab significantly controlled the S phase of ASM cell cycle induced by PDGF-BB. As a consequence, Real time PCR and Western blot revealed the fact that Mab decreased the expression of Drp-1 mRNA and protein, and promoted the expression of Mfn-2 mRNA and protein. These findings suggested that Mab placed restrictions on the proliferation of rat ASMCs induced by PDGF-BB and the mechanism might be associated with the intracellular calcium inhibited and the mitochondrial fission/fusion regulated by Mab., (Copyright © 2019 Elsevier B.V. All rights reserved.)